Heat sealing septum for storage plates

ABSTRACT

An apparatus for sealing fluid containing vessels comprising a sheet of elastomer forming a sealing member having a top and bottom surface, and disposed on a plate containing a plurality of wells for storing fluids. A product that can seal the wells of a multiwell plate, and has the aspects of being vapor resistant, heat sealable, and able to be manipulated by automated analytical equipment. The sealing material is constituted of an elastomer made of synthetic rubber and a layer, comprising a polymer film or a foil attached to one side of the elastomer to form a vapor barrier. The combination of these elements produces a sealing mat that couples the barrier properties of the polymer film or foil with the sealing properties of the elastomer septum.

CLAIM OF PRIORITY

[0001] The present Application claims priority to U.S. ProvisionalApplication No. 60/236,512, filed on Sep. 29, 2000, in the names ofDeborah C. Audino and Gregory R. Martin. The content of the ProvisionalApplication is incorporated herein in its entirety.

FIELD OF INVENTION

[0002] The invention relates to a septum for sealing liquid containingvessels. In particular, the invention relates to an elastomer sheet usedto thermally seal wells of a microtiter test plate used in biological orchemical assays.

BACKGROUND

[0003] Today, the reacting and testing of large numbers of biologicalsamples constitutes a fundamental technique of analysis in modembiological or medical diagnostic science. Specific examples includepolymerase chain reaction (PCR) techniques, radio-immune assay (RIA),enzyme linked immune-sorbent assay (ELISA), enzyme immune assay (EIA),enzyme assays, including receptor binding assays, membrane captureassays, cell washing, and others similar tests. The physical equipmentused to perform these large numbers of required tests efficiently,accurately, and safely, has been for many years the microtiter plates or“microplates,” also known as multiwell plates. Multiwell plates come invarious sizes, from 6 to over 1536 wells. The most typical multiwellplates contain ninety-six (96) molded plastic wells in an 8×12 arraywith a typical volume capacity of about 200 microliters.

[0004] In the striving for ever increasing efficiency and to reducemanually repetitive tasks performed by laboratory technicians, manymulti-sample plates have been adapted for use in automated handlingsystems. Such systems employ multiwell plates for storing, reactingand/or analyzing liquid samples, and typically includes a liquidhandling device, which transfers fluid between selected containersand/or wells, and an automated plate handling apparatus to manipulatemultiwell plates that contain the samples.

[0005] Usually, multiwell plates possess a lid designed to prevent dustor other contaminants from entering the wells, as well as to reduce therate of evaporation. These lids generally are sturdy enough to withstandhandling by the variety of automated scientific instruments and roboticmeans used to remove and replace the lids on the multiwell plates.

[0006] Nevertheless, in several ways the design of the standardmultiwell plate still has some shortcomings. Many multiwell plate lidsfit loosely and are not designed to seal the tops of the open wells.Samples of test compounds being stored in plates need to avoidadsorption of water from the surrounding atmosphere. Samples handled inan automated system may need to be heated and/or agitated at variouspoints during the processing cycle. Such operations normally require thewells containing the samples to be sealed. Liquids can spill out of thewells or aerosols can form during fluid transfers. Liquids escaping fromthe wells, however minute in quantity, can contaminate the analysisbeing performed, and may also create a hazard if the testing involvesinfectious materials. Moreover, condensation tends to form from thewells since the lids do not create a tight seal. Over time, thiscondensation can spread along the lid and drip from one well intoneighboring wells, creating cross-contamination between the samples inthe wells. Thus, the seals typically need to be fluid-tight to preventloss of sample fluid, especially when the contents of a well is heated,creating a positive pressure in the well. Often after the heating and/oragitation step, the plates need to be uncovered in order to add otherreagents, or to extract reacted samples. A case illustrative from therealm of molecular biology—a typical PCR involves cycling liquidsamples, contained within individual wells of a test plate, 30 timesbetween temperatures of about 50° C. to about 94-95° C. During thiscycling process, liquid may evaporate, contributing excessively tocross-talk between the wells. Compounds being stored in hygroscopicsolvents need to avoid adsorption of water so as avoid unintendeddilution or hydrolysis during storage.

[0007] To minimize such evaporation, adsorption, or cross talk,manufactures in the microplate industry have developed a variety ofsealing devices for multiwell plates. Products in the form of tapes andsealing mats are available on the market to cover the wells of amultiwell plate. For example, tapes are typically made of polyester,polypropylene, or a fluoropolymer, and sold by a variety of suppliersincluding Hybaid, Rainin, MJ Research, Techne, Top Flight, and CorningCostar. Sealing mats are typically made from synthetic rubber,polypropylene, or silicone and have a matrix of sealing plugs situatedon one surface of the mat for use in plugging individual wells.

[0008] In the past elastomer mats have depended on either a pressuresystem or a friction fit to mechanically seal the multiwell plates.Examples, such as U.S. Pat. Nos. 5,056,427 (the ‘427 patent), 5,604,130(the ‘130 patent), and 5,853.586 (the ‘586 patent), describe sealingmechanisms that are held to the plate by either a pressure plate or apressure differential. The ‘427 patent claims a tight sealing structurefor use with a reagent tray that suppresses evaporation of fluids duringthermal reactions. A planar, elastic, sealing member is placed on top ofthe tray to cover the openings, and is secured to the reagent tray by apressure plate. Likewise, the ‘130 patent discloses a sealing cover fora multiwell, microtitration plate that uses another pressure apparatus.The cover contains a pad, fashioned from a flexible polymer sheet, and aplurality of resiliently compressible ridges formed on the sheet. Theridges deform when pressure is applied to the cover, which effectivelyforms a fluid-tight seal between the pad and well openings in the plate.When the pressure is released, the ridges rebound sufficiently to theiroriginal form to break the seal. In the ‘586 patent, a flexible sealingmember collapses, in the direction of a filtration vacuum, into eachindividual well of a multiwell plate.

[0009] Although useful in preventing liquid content loss by evaporationor cross-talk, the tapes and mats are not designed for used in automatedassay processes. The materials from which these products are made aretoo thin to be efficiently worked by most automated instruments. Thepolypropylene mats need significant pressure to place and remove them,while the silicone mats are too flimsy for a machine to handle them,requiring a lab worker to manually fit and remove them. Additionally,silicone has too large a free volume and, thus permits free diffusion ofwater or solvent vapors as well other gases through the seal. Hence,there is a need for a cover capable of effectively sealing the wells ofa multiwell plate in an automated system. The seal should prevent theloss of well contents during heating or agitation processes, yet beusable without the need to apply unnecessary force or unduly complexsystems.

SUMMARY OF INVENTION

[0010] The present invention comprises a product that can seal the wellsof a multiwell plate, has the aspects of being vapor resistant, heatsealable, and is able to be manipulated by automated analyticalequipment. The sealing material is constituted of an elastomer made ofsynthetic rubber and a layer, comprising a polymer film or a foilattached to one side of the elastomer to form a vapor barrier.Alternatively, the sealing layer of the invention comprises across-linked elastomer that is laminated to a thermoplastic film. Thecombination of these elements produces a sealing mat that couples thebarrier properties of the polymer film or foil with the sealingproperties of the elastomer septum.

[0011] The invention comprises also a microtiter well plate having sucha sealing material. The bottom surface of the elastomer is sealedthermally to the top surface of the microtiter well plate, in a mannerthat it covers the entire plate.

BRIEF DESCRIPTION OF THE DRAWINGS

[0012]FIG. 1 is a perspective view of one embodiment of the presentinvention showing an elastomer sheet adhered to a multiwell test plateof a standard configuration.

[0013]FIG. 2 is an embodiment of a septum with a laminated structure inwhich a metal foil with a polymer coating on both sides of the foil isattached to an elastomer sheet.

[0014]FIG. 3 is a top-down sequence of the layers of another laminateembodiment comprises: an elastomer sheet, a polymer binder, a metallicfoil, and another polymer layer.

[0015]FIG. 4 is a cross-linked elastomer, having a thickness that islaminated to a thermoplastic film.

[0016]FIG. 5 is an apparatus that alternatively embodies the inventionwherein an elastomer material of a sealing member is set in a liddesigned to fittingly engage a multiwell plate.

[0017]FIGS. 5A and 5B are two variations of a partial cross-sectionalview of an elastomer sealing sheet under a micro-titer plate lid placedover the micro-titer well plate.

[0018]FIG. 6 is an exploded view showing one embodiment of the inventionwith a micro-titer plate lid having a plurality of holes, which extendthrough the material of the lid, and an elastomer sealing sheet arrangedbelow it, ready to be welded to the underside or inner surface of thelid.

[0019]FIG. 6A is a cross-sectional view of part of the lid of amicro-titer plate.

DETAILED DESCRIPTION OF THE INVENTION

[0020] The invention comprises certain elastomers used either alone oras part of a laminated structure for sealing liquid containers, inparticular, for multiwell plates employed in the biological research orpharmaceutical industries. The invention also includes microtiter platedevices having such an elastomer-sealing structure. As currentlyconceived in the most simplistic form, an elastomer film 10 welds to theupper surface 12 of a multiwell plate 14 to produce an integral seal ofeach well 16, as shown in FIG. 1. This is achieved by selecting amaterial of a similar chemical composition, or at least of a compatiblecomposition, as that of the plate's upper surface. Thermoplasticelastomers (TPEs) can be welded to polymers that are similar orcompatible to one of the TPE's phases. The affinity of similar chemicalmaterials increases the strength of the bond between the elastomerseptum and the plate to which it is sealed.

[0021] At the present time, a large number of storage or multiwell testplates are molded out of polypropylene (PP). A compatible TPE such assantoprene®, an elastic material that is made from polypropylene blendedwith ethylene-propylene dienemethylene (EPDM) rubber particles is wellsuited for sealing polypropylene plates. Thus, a santoprene® elastomersheet, for example, can be cut to size and welded thermally quite easilyand securely to the polypropylene substrate. Similarly,styrene-butadiene rubber could weld to styrene made objects. Other TPEsare poly(ester-block-ether) and nylon-block-polyether. These TPE's, aswell as thermoset elastomers, can be joined or laminated to a filmcompatible with the polymer of the plate being sealed. Siliconematerials, although usable, are not as favored as they are highlypermeable for certain applications.

[0022] Elastomers in general have low durometer hardness. By selectivelychoosing materials with the appropriately low durometer hardness andhigh elasticity, any perforation that is made in the elastomer film bypiercing with a syringe needle, a pipette tip, or any other insertionwill close-up again once the insertion is removed. An elastomer materialthat has a durometer value of about 30-70 shore A, such as santoprene®is illustrative. A more preferred hardness is within the range ofbetween about 35-60 shore A. Available from Advanced Elastomer Systems,santoprene® deforms to accommodate the insertion, then rapidly recoversits original shape to close the puncture, preventing either air fromoutside from seeping in or vapors from within each well from leakingout. In an embodiment of the invention, a santoprene® sheet having adurometer value of about 55 shore A was used and found to work well. Theelastomer sheet in a relaxed, non-compressed state will have on averagea thickness of about 0.020 to about 0.130 of an inch. Certain sectionsof an elastomer sheet, however, may be slightly thinner or thicker,contingent on the type of use and the corresponding part or section of atest plate that the sheet will cover and seal. For instance, those partsof the elastomer sheet which engage the tops of inter-well walls of amultiwell plate may be slightly thicker, so as to better bind with theplate, while the parts of the sheet that are immediately over a wellopening may be thinner, to permit ease of penetration by a syringeneedle or pipette tip. This description is in no way limiting to theinvention, since the reverse may also be applicable and a viableembodiment.

[0023] Another embodiment of the septum includes a laminated structurein which a metal foil 18 with a polymer coating 20 a, 20 b on both topand bottom sides of the foil is attached to an elastomer sheet 10, asillustrated in FIG. 2. Some problems at this time with existing sealingmechanisms have partly motivated our decision to combine a polymer witha metallic foil. Previously, seals such as sealing tapes oftencontaminated the samples in wells because solvent splashing onto theunder surface of pressure sensitive adhesive leached contaminants intosamples. A polymeric material combined with a metal foil is betterbecause it is not extractable and can not be affected by solventsleaching. The metal foil also acts as an effective vapor barrier toavoid gas diffusion into or out of the well. For example of the designedfunction, the properties of the elastomer-foil laminate can keepdimethyl sulfoxide (DMSO) solvent in the wells of a multiwell plate,while keeping water, oxygen or other gases out to prevent hydrolysis oroxidation.

[0024] In another embodiment, a laminate of multiple layers comprises,from top to bottom: an elastomer sheet 10, a first polymer binder 21, ametallic foil 18, and a second polymer layer 22. This embodiment isillustrated schematically in FIG. 3. The first polymer coating bonds themetal foil to the elastomer, while the second polymer layer is welded toseal the laminated structure to a storage or test plate, which is thefinal substrate. A heating block, such as a platten, can be used tosupply heat through the elastomer to the surface of the well-plate so asto melt the second polymer layer against the interface of the plate. Forinstance, a santoprene® elastomer will bind to a polypropylene coatingon one side of the foil, while the same or another type of polymerapplied on the other side of the foil is left free to adhere to thesurface of the plate. So as not to deform or damage the underlying testplate, the adhesive polymer that is selected will ideally soften andmelt at a temperature lower than that for polypropylene compounds.Typically, a polypropylene test plate melts between about 160° C. toabout 189° C. Consequently, the adhesive polymer will ideally soften ormelt at a temperature at or below about 157° C. Other adhesive polymersthat can be used include any grade of polypropylene with a lower meltingtemperature. Test plates made from polystyrene, which melts betweenabout 240-250° C., can better tolerate slightly higher temperatures.

[0025] When using a tie layer between an elastomer and test platesurface, most ideally the tie layer will melt first, before the testplate material starts to soften. First, the best seal is achieved whenboth faces melt just enough to have physical entanglements of thepolymers. But desiring to minimize heat exposure heat history to workingbiological samples contained within, a second type of seal can beachieved when we use materials that melt at a lower temperature to avoidplate deformation. These kinds of materials, nonetheless, still havegood sealing properties.

[0026] A co-polymer such as Plexar™ may be employed to make a hot-meltadhesive with good adhesion properties between the metal foil and theplate. Plexar™ is poly(ethylene-co-maleic anhydride), and commerciallyavailable from Equistar. The polar maleic anhydride functionalizes thepolymer to make it stick to metal. Plexar™ film is mentionedspecifically, as it will stick to both metals and santoprene®. Otherco-polymers that may work to stick metal foils to the plate includematerials that contain vinyl acetate and the like. This compositestructure will enhance the sealing properties of the elastomer with thebarrier properties of the metal foil. Any monomer that has highly polargroups can produce good adhesion.

[0027] It is envisioned that elastomer materials or polymer films havingchemical compositions that are only partially compatible with thematerial of a multiwell test plate will permit us to create releasableseals. That is, once a elastomer sheet adheres to the test platematerial, any incompatibility of the polymer film will allow releasewhen force is applied to pull the sheet off. Generally, the lesscompatible the sheet is with the plate or lid material the less likelythe sheet will bond securely with the plate or lid. Therefore, up to acertain point, by selectively employing partially compatible polymers,we can more likely make peelable seals.

[0028] In an alternative embodiment, the layers of the laminate cancomprise: an elastomer sheet, a metal foil and another polymer layer.The polymer coating between the elastomer sheet and metal foil can beomitted when direct lamination of the foil to elastomer is achieved.Also, if a cross-linked elastomer is used, then the lower layer of alaminate would need to be a thermoplastic polymer that is compatiblewith or the same as the material of the underlying microplate (such aseither polypropylene or polystyrene), since the cross-linked elastomeritself can't be melted to form a seal. Examples of cross-linkedelastomer materials suitable for use with the invention include butylrubbers, that have low permeability to air, neoprene, that imparts goodchemical resistance, and other like materials, including Buna-N orbetter termed as nitrile rubber (i.e.,poly(acrylonitrile-co-1,3-butadiene)). As mentioned before, siliconealso can be used but it is least desirable. As illustrated in FIG. 4, across-linked elastomer 24 having a thickness of about 0.20-0.130 inchesis laminated to a thermoplastic film 26 having a thickness that is asthin as possible, possibly about 0.001-0.004 inches. A metalic foillayer 18 could also be sandwiched between the elastomer andthermoplastic layers to provide possibly a better vapor barrier. Anotheroption is to omit the foil layer entirely. It is believed that thesecross-linked variations of the present invention can be important sincethese designs for a sealing septum may be much more commerciallypractical. Preferred embodiments may include, for example, thefollowing. For sealing polypropylene (PP) plates, a polypropylene filmor compatible material is corona treated on one side. This side iscoated with a layer of partially epoxydized polybutadiene (PolyBD 605Eresin from Sartomer) with a dissolved (1-4% prefered) cationicphotoinitiator (SarCat K185 from Sartomer). The polybutadiene thenpolymerizes to form a cross-linked elastomer (like a thermoset) that isbonded to the thermoplastic film. For sealing polystyrene plates, likethat for PP, above, except that the thermoplastic film that is coronatreated would be a polystyrene film or compatible material.

[0029] The invention is embodied by an apparatus for sealing fluidcontaining vessels. In its broadest iteration, the apparatus comprises asheet of elastomer forming a sealing member having a top and bottomsurface, disposed on a plate containing a plurality of wells for storingfluids, and the sealing member is thermo-chemically bonded to the plate,wherein the elastomer has a propensity to reseal after being punctured.The elastomer is made of a thermoplastic polymer material.Alternatively, the elastomer can be made of a thermosetting polymerjoined or laminated to a film having a chemical affinity to the plate'schemical composition.

[0030] An apparatus that alternatively embodies the invention comprisessetting an elastomer material of the sealing member in a lid 30 designedto fittingly engage a multiwell plate 14. FIGS. 5 shows a perspectiveview of such an apparatus. The lid 30 has several openings 32 thatconform to the arrangement of micro-titer wells. FIGS. 5A and 5B showtwo variations of a partial cross-sectional view of a micro-titer platewith a cover 34 and elastomer seal 36 configured over one well 38. InFIG. 5A, the lid is open 39 over the well, like as shown in FIGS. 6 and6A. In FIG. 5B the lid is one solid piece without any holes extendingthrough the lid material. In FIG. 5A, the well underneath the elastomerseal may be accessed through the elastomer with, for instance, a syringeor pipette tip. The elastomer self-seals once the intrusion is removed.

[0031]FIG. 6 shows an exploded, perspective view of a microtiter platecover or lid 30 having a top surface 40 and a descending skirt 42 orsidewall with a plurality of holes 44, extending through the lidmaterial, arranged in the format of a 96-well plate. An elastomersealing film 10 of an embodiment described herein is located under thelid 30. FIG. 6A is a partial cut-away view of the lid shown in FIG. 6.

[0032] An elastomer could be either molded as part of a polypropylenelid or welded in a secondary operation to the lid. No glue or otherpolymer adhesive is employed to engage or adhere the elastomer sheet tothe lid. Rather an elastomer, like santoprene®, directly welds with thepolypropylene material of the underside of the lid or top surface of theplate. Melting at the interface between the lid or plate and thethermoplastic elastomer achieves the seal. Other ways of attaching theseptum can include insert molding the seal by injecting the elastomermaterial onto the plate for lids that that have access openings.Variations in the type of elastomer used are also possible so long asthese materials can directly bond with the material of the plate or lid.

[0033] The lid is in the form of a substantially rectangular rigid framethat has a top and bottom surface and is surrounded by a peripheralskirt. FIG. 6 is an exploded view of another embodiment of the presentinvention. The bottom of the lid holds an elastomer sheet, which issized to fit within the confines of the peripheral skirt, flush againstthe top of a multiwell plate.

[0034] The dimensions of the lid are preferably sized such that theouter skirt section of the frame will fit over an industry standard 96well plate. The skirt section preferably extends perpendicularly fromthe outer frame periphery. This skirt section helps to center the frameover a multiwell plate and preferably extends approximately 0.4 cm fromthe frame's top surface. Furthermore, the skirt section serves as asuitable region for a clamping device from an automated roboticextension to attach in order to secure the lid to a plate, orconversely, to remove the lid from a plate.

[0035] The size of the lid frame should be compatible with plates thatfit into PCR equipment that are currently available such as the GENE AMP9600 manufactured by Perkin Elmer, or the DNA ENGINE PTC 200 made by MJResearch. Preferably, the outer dimensions of the frame areapproximately 8.5 cm×12.5 cm. But, not withstanding this preference, theframed seal does not have to be limited to use for PCR plates, ratherits dimensions can be changed to fit any multiwell plate.

[0036] The top surface of the lid has a matrix of holes extendingthrough it. The holes permit access to individual wells through theelastomer sheet by means of a needle, pipette tip, or other penetratingdevice. The holes in the lid are designed to correspond to the number ofwells in a corresponding microplate, i.e., 48, 96, 384, 1536, etc.Preferably the holes are arranged in a matrix of mutually perpendicular8 and 12 holerows for use with a 96 well plate.

[0037] Therefore to recapitulate, our invention is an apparatus forsealing fluid containing vessels comprising a sheet of elastomer forminga sealing member having a top and bottom surface, and disposed on aplate containing a plurality of wells for storing fluids. The sealingmember is thermally bonded to the plate, wherein the elastomer has apropensity to reseal after being punctured. In one variation, theelastomer is made of a thermoplastic polymer material. Another way ofcharacterizing the elastomer is that it is made of a thermosettingpolymer laminated to a film having an affinity to the plate's chemicalcomposition or is laminated to a film that is compatible to said plate'scomposition. In one version, the apparatus also has a film of elastomerhaving a top and bottom surface, bonded to a metallic foil on at leastone of said surfaces. The foil is thermally sealable to a multiwell testplate, wherein the elastomer and foil together make a vapor resistantbarrier. The elastomer is thermally sealed to said test plate by meansof heat bonding a compatible polymer between said metallic foil and saidtest plate. Another iteration of the invention, is an apparatuscomprising a film of elastomer having a top and bottom surface, bondedto a polymer film on at least one of said surfaces, and the polymer filmis likewise, thermally sealed to a multiwell test plate. The elastomerand polymer film together also make a vapor resistant barrier.

[0038] In an alternative embodiment, our invention is an apparatuscomprising a planar sealing member composed of elastic material anddisposed on a test plate having a plurality of fluid receiving wells. Ametallic foil or polymer film is adhered to the planar sealing member. Arigid lid defined by a peripheral skirt and a top and bottom surfacehaving a predetermined matrix of openings with extending through, isattached to the test plate and the openings correspond to the wells inthe plate. Alternatively, the lid has a single large rectangularopening. The sealing member and metallic foil or polymer film is eithermolded or welded to said bottom surface, with the sealing member indirect contact with the bottom surface, and the metallic foil or polymerfilm as a barrier layer exposed toward the open wells in the test plate.The polymer film or metallic foil is heat sealed to the plate. Apolymer, that is compatible with the plate's chemical composition,adheres the metallic foil to the plate by thermally bonding.

[0039] The apparatus is can also be characterized by having an elastomermade of a thermoplastic polymeric compound chosen from the groupconsisting of: an elastic material that is made from polypropyleneblended with ethylene-propylene diene methylene (EPDM) rubber particles,styrene-butadiene, poly(ester-block-ether), or nylon-block-polyether.Alternatively, the elastomer is made of a cross-linked polymericcompound chosen from the group consisting of: polybutadiene,cross-linked epoxidized polybutadiene, ethylene-propylene dienemethylene (EPDM), polyisobutylene, polychloroprene (neoprene),cis-1,4-polyisoprene, polyurethane, nitrile rubber (Buna-N),epichlorohydrin rubber, silicone block copolymers or silicone. Moreparticularly, the elastomer can be made of a polypropylene blended withEPDM rubber particles. The elastomer can be hydrophobic. The elastomer'slower surface has a chemical composition that is totally compatible toform a bond with said plate's chemical composition, thereby creating anon-releasable seal; or, the elastomer's lower surface has a chemicalcomposition that is partially compatible to form a bond with saidplate's chemical composition, thereby creating a releasable seal.

[0040] The apparatus can have a base test plate made from polypropyleneor polystyrene. The compatible polymer is of a chemically similarcomposition as that of said test plate. More particularly, a specificembodiment uses a compatible polymer that is poly(ethylene-co-maleicanhydride). The compatible polymer melts at a lower temperature than atemperature at which said test plate begins to deform. Hence, theheating temperature is at or below about 165-160° C., preferably about157° C. or below.

[0041] Our invention also incorporates a method of sealing a fluidcontainer comprising the following steps:

[0042] a) providing a roll of film made of an elastomer having a top andbottom surface, the bottom surface is bonded to a layer comprising ametallic foil or a thermoplastic film that is compatible with thepolymer material of a microtiter test plate, and a test plate having aplurality of wells located in a top surface of said test plate; b)cutting an unrolled roll of said elastomer film, wherein each cut pieceof film corresponds with the length and width dimensions of said topsurface of said test plate, whereby each well in said test plate iscovered by said elastomer film; c) disposing planarly said cut piece offilm onto said top surface of said test plate; d) affixing said cutpiece of film to said top surface of said test plate, whereby each wellin said test plate is covered by said elastomer film; e) applying heatto said cut piece of film to thereby thermo-chemically bond said cutpiece of film to said top surface of test plate.

[0043] Although a preferred embodiment of the invention has beendisclosed in detail for the purpose of illustration, those skilled inthe art can appreciate that variations or modifications may be madethereof and other embodiments may be perceived without departing fromthe scope of the invention, as defined by the appended claims and theirequivalents.

We claim:
 1. An apparatus for sealing fluid containing vesselscomprising: a sheet of elastomer forming a sealing member having a topand bottom surface, disposed on a plate containing a plurality of wellsfor storing fluids, and said sealing member is thermally bonded to saidplate, wherein said elastomer has a propensity to reseal after beingpunctured.
 2. An apparatus for sealing fluid containing vessels of claim1, wherein said elastomer is made of a thermoplastic polymer material.3. An apparatus for sealing fluid containing vessels of claim 1, whereinsaid bottom surface of said elastomer is made of a thermosetting polymerhaving a chemical affinity to said plate's chemical composition.
 4. Anapparatus for sealing fluid containing vessels of claim 1, wherein saidelastomer is joined to a film that is compatible to said plate'scomposition.
 5. An apparatus for sealing fluid containing vesselscomprising: a) a film of elastomer having a top and bottom surface,bonded to b) a metallic foil on at least one of said surfaces, and c)said foil is thermally sealable to a multiwell test plate, wherein saidelastomer and foil together make a vapor resistant barrier.
 6. Anapparatus for sealing fluid containing vessels of claim 5, wherein saidelastomer is thermally sealed to said test plate by means of heatbonding a compatible polymer between said metallic foil and said testplate.
 7. An apparatus for sealing fluid containing vessels comprising:a) a film of elastomer having a top and bottom surface, bonded to b) apolymer film on at least one of said surfaces, and c) said polymer filmis thermally sealed to a multiwell test plate, wherein said elastomerand polymer film together make a vapor resistant barrier.
 8. Anapparatus for sealing fluid containing vessels of anyone of claims 1, 4,or 5, wherein said elastomer is made of a thermoplastic polymericcompound chosen from the group consisting of: an elastic material thatis made from polypropylene blended with ethylene-propylene dienemethylene (EPDM) rubber particles, styrene-butadiene,poly(ester-block-ether), or nylon-block-polyether.
 9. An apparatus forsealing fluid containing vessels of anyone of claims 1, 3, 4, 5 or 7,wherein said elastomer is made of a cross-linked polymeric compoundchosen from the group consisting of: polybutadiene, cross-linkedepoxidized polybutadiene, ethylene-propylene diene methylene (EPDM),polyisobutylene, polychloroprene (neoprene), cis-1,4-polyisoprene,polyurethane, nitrile rubber (Buna-N), epichlorohydrin rubber, siliconeblock copolymers or silicone.
 10. An apparatus for sealing fluidcontaining vessels of anyone of claims 1, 3, 4, 5 or 7, wherein saidelastomer is hydrophobic.
 11. An apparatus for sealing fluid containingvessels of anyone of claims 1, 3, 4, 5 or 7, wherein said elastomer'slower surface has a chemical composition that is totally compatible toform a bond with said plate's chemical composition, thereby creating anon-releasable seal.
 12. An apparatus for sealing fluid containingvessels of anyone of claims 1, 3, 4, 5 or 7, wherein said elastomer'slower surface has a chemical composition that is partially compatible toform a bond with said plate's chemical composition, thereby creating areleasable seal.
 13. An apparatus for sealing fluid containing vesselsof anyone of claims 3 4, or 5, wherein said compatible polymer is of achemically similar composition as that of said test plate.
 14. Anapparatus for sealing fluid containing vessels of anyone of claims 3, 4,or 5, wherein said compatible polymer is poly(ethylene-co-maleicanhydride).
 15. An apparatus for sealing fluid containing vessels ofclaim 1 or 5, wherein said elastomer is made of a polypropylene blendedwith EPDM rubber particles.
 16. An apparatus for sealing fluidcontaining vessels of anyone of claims 3, 4, or 5, wherein said testplate is made from polypropylene.
 17. An apparatus for sealing fluidcontaining vessels of anyone of claims 3, 4, or 5, wherein said testplate is made from polystyrene.
 18. An apparatus for sealing fluidcontaining vessels of anyone of claims 3, 4, or 5, wherein saidcompatible polymer melts at a lower temperature than a temperature atwhich said test plate begins to deform.
 19. An apparatus for sealingfluid containing vessels of claim 18, wherein said lower temperature isat or lower than 165° C.
 20. A method of sealing a fluid containercomprising the following steps: a) providing a roll of film made of anelastomer having a top and bottom surface, the bottom surface is bondedto a layer comprising a metallic foil or a thermoplastic film that iscompatible with a polymer material of a microtiter test plate, and saidtest plate having a plurality of wells located in its top surface; b)cutting an unrolled roll of said film, wherein each cut piece of filmcorresponds with the length and width dimensions of said top surface ofsaid test plate, whereby each well in said test plate is covered by saidfilm;. c) disposing planarly said cut piece of film onto said topsurface of said test plate; d) affixing said cut piece of film to saidtop surface of said test plate, whereby each well in said test plate iscovered by said film; e) applying heat to said cut piece of film tothereby thermo-chemically bond said cut piece of film to said topsurface of test plate.
 21. An apparatus for sealing fluid containingvessels comprising: a) a planar sealing member composed of elasticmaterial and disposed on a plate having a plurality of fluid receivingwells; b) a metallic foil laminated to said planar sealing member; c) arigid lid defined by a peripheral skirt and a top and bottom surfacehaving a predetermined matrix of openings extending through, and saidopenings correspond to said wells in said plate; d) wherein said sealingmember and metallic foil laminate is either molded or welded to saidbottom surface, with said sealing member in direct contact with saidbottom surface and said metallic foil exposed toward said open wells insaid plate, and said metallic foil is heat sealed to said plate.
 22. Anapparatus for sealing fluid containing vessels of claim 21, wherein apolymer, that is compatible with said plate's chemical composition,adheres said metallic foil to said plate by thermally bonding.
 23. Anapparatus for sealing fluid containing vessels of claim 21, wherein saidmatrix of openings is 96 holes.
 24. An apparatus for sealing fluidcontaining vessels of claim 21, wherein said matrix of openings is 384holes.
 25. An apparatus for sealing fluid containing vessels of claim21, wherein said matrix of openings is 1536 holes.
 26. An apparatus forsealing fluid containing vessels of claim 21, wherein said lid has asingle large rectangular opening.
 27. A microtiter plate having aplurality of fluid receiving wells comprising a planar sealing membercomposed of an elastomer material and disposed on said plate; a metallicfoil laminated to said planar sealing member; a thermoplastic film; arigid lid defined by a peripheral skirt and a top and bottom surfacehaving a predetermined matrix of openings extending through, and saidopenings correspond to said wells in said plate; wherein said sealingmember and metallic foil laminate is either molded or welded to saidbottom surface, with said sealing member in direct contact with saidbottom surface and said metallic foil exposed toward said open wells insaid plate, and said metallic foil is heat sealed to said plate.
 28. Themicrotiter plate of claim 27, wherein a polymer, that is compatible withsaid plate's chemical composition, adheres said metallic foil to saidplate by thermally bonding.
 29. The microtiter plate of claim 27,wherein said matrix of openings is 96 holes.
 30. The microtiter plate ofclaim 21, wherein said matrix of openings is 384 holes to-1536 holes.31. The microtiter plate of claim 27, wherein said lid has a singlelarge rectangular opening.